Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice
Abstract Objective This study was aimed to measure the effects of a high-fat diet and metformin on placental mechanistic target of rapamycin (mTOR) signaling in mice. Study Design Pregnant friend virus B (FVB)-strain mice were allocated on embryonic day (e) 0.5 to one of fo...
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Format: | Article |
Language: | English |
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Thieme Medical Publishers, Inc.
2019-04-01
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Series: | American Journal of Perinatology Reports |
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Online Access: | http://www.thieme-connect.de/DOI/DOI?10.1055/s-0039-1683362 |
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author | Matthew R. Grace Sarah K. Dotters-Katz Chunxiao Zhou Tracy Manuck Kim Boggess Victoria Bae-Jump |
author_facet | Matthew R. Grace Sarah K. Dotters-Katz Chunxiao Zhou Tracy Manuck Kim Boggess Victoria Bae-Jump |
author_sort | Matthew R. Grace |
collection | DOAJ |
description | Abstract
Objective This study was aimed to measure the effects of a high-fat diet and metformin on placental mechanistic target of rapamycin (mTOR) signaling in mice.
Study Design Pregnant friend virus B (FVB)-strain mice were allocated on embryonic day (e) 0.5 to one of four groups; group 1: control diet (CD, 10% fat) + control treatment (CT), group 2: CD + metformin treatment (MT), group 3: high-fat diet (HFD, 60% fat) + CT, and group 4: HFD + MT. Metformin (2.5 mg/mL) was provided in water; CT mice received water. Fetuses and placentas were collected. Western blot measured placental p-Akt and p-S6 expression.
Results 20 dams (five/group) and 192 fetuses were studied. Compared with CD-fed, HFD-fed dams had higher placental p-Akt protein expression (p < 0.0001). Among HFD-dams, placental p-Akt was higher in metformin-treated compared with control-treated (p < 0.001). Among CD-fed dams, there was no significant difference in placental p-S6 expression in MT versus CT groups. Among HFD-fed dams placental p-S6 expression was lower in those exposed to metformin-treated versus controls (p = 0.001).
Conclusion Increased placental mTOR signaling and metformin inhibition of placental mTOR signaling only occurred in the presence of an HFD exposure. These findings suggest that metformin may modulate placental mTOR signaling in the presence of metabolic exposures during pregnancy. |
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institution | Directory Open Access Journal |
issn | 2157-6998 2157-7005 |
language | English |
last_indexed | 2024-12-12T00:21:20Z |
publishDate | 2019-04-01 |
publisher | Thieme Medical Publishers, Inc. |
record_format | Article |
series | American Journal of Perinatology Reports |
spelling | doaj.art-0a55b23d496f4ffaa704678b8f3edfe82022-12-22T00:44:43ZengThieme Medical Publishers, Inc.American Journal of Perinatology Reports2157-69982157-70052019-04-010902e138e14310.1055/s-0039-1683362Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in MiceMatthew R. Grace0Sarah K. Dotters-Katz1Chunxiao Zhou2Tracy Manuck3Kim Boggess4Victoria Bae-Jump5Tennessee Maternal Fetal Medicine and the University of Tennessee, Division of Obstetrics and Gynecology, Department of Clinical Medicine Education, Nashville, TennesseeDivision of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Duke University, Durham, North CarolinaDivision of Gynecologic Oncology, University of North Carolina School of Medicine, Chapel Hill, North CarolinaDivision of Maternal–Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, North CarolinaDivision of Maternal–Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, North CarolinaDivision of Gynecologic Oncology, University of North Carolina School of Medicine, Chapel Hill, North CarolinaAbstract Objective This study was aimed to measure the effects of a high-fat diet and metformin on placental mechanistic target of rapamycin (mTOR) signaling in mice. Study Design Pregnant friend virus B (FVB)-strain mice were allocated on embryonic day (e) 0.5 to one of four groups; group 1: control diet (CD, 10% fat) + control treatment (CT), group 2: CD + metformin treatment (MT), group 3: high-fat diet (HFD, 60% fat) + CT, and group 4: HFD + MT. Metformin (2.5 mg/mL) was provided in water; CT mice received water. Fetuses and placentas were collected. Western blot measured placental p-Akt and p-S6 expression. Results 20 dams (five/group) and 192 fetuses were studied. Compared with CD-fed, HFD-fed dams had higher placental p-Akt protein expression (p < 0.0001). Among HFD-dams, placental p-Akt was higher in metformin-treated compared with control-treated (p < 0.001). Among CD-fed dams, there was no significant difference in placental p-S6 expression in MT versus CT groups. Among HFD-fed dams placental p-S6 expression was lower in those exposed to metformin-treated versus controls (p = 0.001). Conclusion Increased placental mTOR signaling and metformin inhibition of placental mTOR signaling only occurred in the presence of an HFD exposure. These findings suggest that metformin may modulate placental mTOR signaling in the presence of metabolic exposures during pregnancy.http://www.thieme-connect.de/DOI/DOI?10.1055/s-0039-1683362metforminmtormicehigh-fat diet |
spellingShingle | Matthew R. Grace Sarah K. Dotters-Katz Chunxiao Zhou Tracy Manuck Kim Boggess Victoria Bae-Jump Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice American Journal of Perinatology Reports metformin mtor mice high-fat diet |
title | Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice |
title_full | Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice |
title_fullStr | Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice |
title_full_unstemmed | Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice |
title_short | Effect of a High-Fat Diet and Metformin on Placental mTOR Signaling in Mice |
title_sort | effect of a high fat diet and metformin on placental mtor signaling in mice |
topic | metformin mtor mice high-fat diet |
url | http://www.thieme-connect.de/DOI/DOI?10.1055/s-0039-1683362 |
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